rs121908318

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP5_Moderate

The ENST00000246515.2(SLURP1):c.43T>C(p.Trp15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,612,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SLURP1
ENST00000246515.2 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.100

Variant links:

Genes affected

SLURP1 (HGNC:18746): (secreted LY6/PLAUR domain containing 1) The protein encoded by this gene is a member of the Ly6/uPAR family but lacks a GPI-anchoring signal sequence. It is thought that this secreted protein contains antitumor activity. Mutations in this gene have been associated with Mal de Meleda, a rare autosomal recessive skin disorder. This gene maps to the same chromosomal region as several members of the Ly6/uPAR family of glycoprotein receptors. [provided by RefSeq, Jul 2008]

SLURP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP5

Variant 8-142742343-A-G is Pathogenic according to our data. Variant chr8-142742343-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 4605.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-142742343-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLURP1	NM_020427.3 linkuse as main transcript	c.43T>C	p.Trp15Arg	missense_variant	1/3	ENST00000246515.2	NP_065160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLURP1	ENST00000246515.2 linkuse as main transcript	c.43T>C	p.Trp15Arg	missense_variant	1/3	1	NM_020427.3	ENSP00000246515	P1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000802

AC:

AN:

249320

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135440

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1460608

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000383

Gnomad4 NFE exome

AF:

0.0000540

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000166

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000124

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Acroerythrokeratoderma

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 2003	- -
Pathogenic, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 29, 2018	The p.Trp15Arg variant in SLURP1 has been reported 13 homozygous and 3 compound heterozygous individuals with clinical features of Mal de Meleda and segregated with disease in 9 affected releatives from at least 2 families (Eckl 2003, Nelle n 2013, Zhao 2014). This variant has been identified in 19/125816 European chrom osomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute. org) and has been reported in ClinVar (Variation ID 4605). In vitro functional s tudies provide some evidence that the p.Trp15Arg variant may impact protein func tion (Favre 2007). In summary, this variant meets criteria to be classified as p athogenic for autosomal recessive Mal de Meleda based upon segregation studies a nd functional evidence. ACMG/AMP criteria applied: PM3_Strong, PP1_Strong, PS3_S upporting. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

0.0033

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.21

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.27

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.0000054

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.56

Sift

Benign

0.14

Sift4G

Benign

0.27

Polyphen

0.81

Vest4

0.39

MutPred

0.85

Gain of methylation at W15 (P = 0.0101);

MVP

0.49

MPC

0.63

ClinPred

0.043

GERP RS

0.80

Varity_R

0.19

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over